Dimethyl fumarate, a dimethyl ester of fumaric acid is chemically known as dimethyl (E) butenedioate. It is marketed under the trade name Tecfidera by Biogene and is a FDA approved drug for the treatment of multiple sclerosis. Dimethyl fumarate has also found applications in organ transplant treatment to reduce or suppress the rejection by the recipient.
General synthetic approach reported for the production of dimethyl fumarate involves the esterification of fumaric acid to the diester in presence of an acid catalyst. WO 2012/170923 describes the synthesis of the dimethyl fumarate by the sulphuric acid catalyzed esterification of fumaric acid. However, the esterification of fumaric acid in presence of sulphuric acid and methanol generates dimethyl sulphate as the by-product, which is a known genotoxic impurity.
Other methods reported for the synthesis of dimethyl fumarate are by the isomerization of the dimethyl maleate using different catalyst such as fumaryl chloride, triphenyl phosphine, thiourea, transition metal catalyst etc.
Most of the reported procedures are not suitable for the commercial scale production of dimethyl fumarate. In order to overcome the problems associated with prior art, there is a need to develop an efficient and cost effective method for the commercial scale production of dimethyl fumarate.